The invention relates to brachytherapy, which is a specialty within the medical field of radiation oncology. More particularly, it relates to the designs of the small radioactive sources used in interstitial brachytherapy.
Such sources are surgically implanted, temporarily or permanently, in close proximity to diseased tissue about to undergo treatment by the radiation emissions from the sources. Usually, a brachytherapy procedure involves many sources implanted throughout the affected tissue mass. (Note: the prefix brachy in the word brachytherapy is from the Greek work brachys, meaning close or short).
Interstitial brachytherapy sources may be of solid, unitary construction and entirely composed of bio-compatible materials, or they may be composed of radioactive and other materials sealed inside bio-compatible capsules or coatings. Outwardly, they are usually metal cylinders with dimensions in the ranges: length 2 to 5 millimeters and diameter 0.2 to 1 millimeters. They rely for their effectiveness upon the photon radiations, i.e. X-rays and gamma-rays, emitted by certain radioisotopes. The amount of radioactivity contained by each source can vary from 0.1 to 100 millicuries (mCi) but is usually in the range 0.5 to 10 millicuries.
Brachytherapy has been practiced since early this century, starting shortly after the discovery of radium by the Curies in 1898. Many different source types have been developed over the intervening years. These have been based upon radioisotopes widely ranging in their half-lives and emission energies, and manufacturing processes have correspondingly varied. Over the last few decades, most sources have been made by irradiating preformed, solid, unitary "seeds" with neutrons in nuclear reactors. (Note: finished interstitial brachytherapy sources ready for implant are often called seeds, but here the word seed is used in the sense of a preformed solid substrate which is not yet made radioactive to any degree, or is in the process of being made fully radioactive for purposes of making a finished brachytherapy source). This simple and economical approach yields unencapsulated radioactive sources in batch sizes on the order of 10,000 units ready for use without further processing. The most prevalent of this type have been iridium-192 sources, which are made from iridium-platinum alloy seeds. These are generally employed as temporary implants. Although somewhat in decline because the energies of their emissions are now considered to be higher than desirable for many applications, iridium-192 sources are still used in the largest numbers in interstitial brachytherapy.
Within the last ten years, other trends have become clearly apparent. There are strong preferences developing in favor of permanent implant sources and radioisotopes emitting only low-energy photon radiations and having half-lives in the 10 to 100 day range. The main reasons for the change in outlook are: a) permanent implants involve only a single surgical procedure and result in lower hospital costs because of short patient stays with no delays or returns for implant removals; b) low photon energies mean less penetrating power, leading to less radiation exposure of healthy tissue surrounding the diseased tissue region, as well as greatly reduced cumulative radiation doses to hospital personnel; and c) half-lives in the 10 to 100 day range allow the right amount of radiation to be delivered at a rate close to optimum with respect to therapeutic effect.
The two main low-energy sources in commercial supply, and now dominating the overall brachytherapy source market in monetary terms, are encapsulated types with radioactive contents sealed inside welded titanium capsules. One type is base don the radioisotope palladium-103 (half-life 17 days) and the other on iodine-125 (half-life 60 days). Of all radioisotopes, these two appear to be by far the most suited for interstitial brachytherapy applications and are not likely to be easily supplanted. Although these source types do possess the virtues delineated for low-energy sources in the preceding paragraph, both are far from ideal in other important respects: a) both are much more expensive and physically larger than the sources being displaced; b) the encapsulation material strongly attenuated the low-energy radiation output; and c) because they are essentially quasi line sources (as opposed to theoretical line sources which have length but no thickness) and their emissions are of low-energy, their radiation output distributions are anisotropic (i.e. lacking in equality in all directions) and this negatively effects treatment planning and outcome. These deficiencies stem largely from their designs and manufacturing methods.
The sequestering and encapsulation of radioactive materials in small containers for brachytherapy purposes are described in U.S. Pat. Nos. 1,753,287; 3,351,049; 4,323,055; 4,702,228; 4,891,165; 4,994,013; 5,342,283; and 5,405,309, which patents are incorporated herein by reference. With the exception of U.S. Pat. No. 1,753,287, these description taken together summarize the technologies developed to date or formally envisioned for the commercial, large scale production of low-energy brachytherapy sources based on palladium-103 and iodine-125.
With regard to the more prevalent low-energy brachytherapy source types, the structures and degrees of anisotropy are indicated in Chapter 1 of the textbook "Interstitial Brachytherapy--Physical, Biological and Clinical Considerations", Interstitial Collaborative Working Group, Raven Press, New York (1990), ISBN 0-88167-581-4. This textbook is incorporated herein by reference. The output radiation fluxes are shown to fall away steeply at the ends of the sources, caused by absorption of the low-energy photon radiations within the sources themselves. Much of this effect stems from a feature of all real line sources. Descriptively, this feature is the longer average path through the substrate and/or encapsulation materials that must be traveled by the radiation directed towards the ends of real line sources. In the cases of currently available encapsulated low-energy brachytherapy sources, the problem is exacerbated by the fact that the sources are welded at the ends, thereby thickening the capsule walls at these locations.
It should be noted that anisotropy of radiation output is generally not a problem as far as treating tissue lying very close to a low-energy brachytherapy source is concerned. At short distances from the source in any direction, say less than one source length, sufficient radiation dose is delivered regardless of anisotropy. However, the radiation flux diminishes quickly with distance from a source and anisotropy becomes an important factor further out from an implanted source where the radiation dose delivered is calculated to be just adequate for that source to play its part in killing the treated tissue mass. The problem is further complicated when there are large uncertainties in planned treatment parameters caused by variations in the degree of anisotropy between individual sources and uncertainties in the orientation of individual sources within an array of sources.
The problem of anisotropy and the contribution to it by end welds and other sorts of seals was appreciated by the patentees of U.S. Pat. Nos. 3,351,049 and 4,323,055 in relation to iodine-125 sources. These related disclosures envisioned cylindrical metal capsules having closed, rounded ends, with the walls at the ends being smooth and symmetric and having a thickness similar to the side walls. However, this idealized construction was never realized in routine practice, the ends of the production sources being simply sealed by thick bead welds.
Some progress in the area was described in U.S. Pat. Nos. 4,702,228 and 5,405,309 respectively in relation to palladium-103 sources. These related disclosures propose the use of metal tube capsules with laser welded end caps, the tube wall and end cap thicknesses being similar. As well as having thin walled welded end caps, the radioactivity distribution is not uniform along the length, but is somewhat biased towards the ends, which should also promote isotropy at the ends. But again, good isotropy is not evident in these sources. Another capsule designed with improved source isotropy in mind is described in U.S. Pat. No. 4,891,165. This disclosure described cylindrical metal capsules formed by press fitting together two, three or four tightly inter-fitting sleeves, each with one end open and one end closed, to yield finished capsules with laminated walls of essentially uniform thickness all around. As disclosed, the capsules were designed to have flat closed ends and to be optionally sealed by an adhesive or by welding. In practice, two sleeves are used and the design has been modified to have rounded ends. The capsule is used with an internal iodine-125 substrate that distributes the radioactivity uniformly along the length of the source as described in U.S. Pat. No. 4,994,013. The modified design is a means of achieving an essentially cylindrical capsule that has uniform wall thickness all around and to have rounded, smooth, symmetric, closed ends as originally disclosed in U.S. Pat. No. 3,351,049. In practice, the capsule of U.S. Pat. No. 4,891,165 is sealed by performing a circumferential weld close to one end where the rim of the formerly open end of the outer cylinder rests against the side wall of the inner cylinder. A study reported in Medical Physics, Vol. 19, No. 4, pp. 927-931 (1992), incorporated herein by reference, indicates that a significant improvement in isotropy is gained by means of this technology, although it is not clear whether welded or non-welded capsules were used in the study. There are perceived problems with this technology, however. Because of the lack of a heat sink behind the weld area, there is a high potential for severely weakening or even perforating the capsule wall in performing the circumferential weld. Another perceived problem due to the lack of a heat sink behind the weld area, is the heating of the internal radioactive substrates, resulting in releases of volatile radioactive iodine and blow-outs during welding before the seal is complete. Yet another perceived problem is that the weld is near one end of the source, resulting in some contribution to source anisotropy because of attenuation of the low-energy radiation.